A compound having a structure represented by the following general formula (1) has excellent antimycotic activity. Luliconazole is a compound having the structure represented by the general formula (1) where both of R1 and R2 are chlorine atoms. The compound having the structure represented by the following general formula (1) such as luliconazole has excellent antimycotic activity, and hence it has been pointed out that the compound is also applicable for treatment of onychomycosis, which has been considered to be untreatable by external application (e.g., see Patent document 1). However, in the case of producing a preparation for treating such onychomycosis, it has been desired to further increase the content of the compound represented by the general formula (1). In particular, in a preparation for treating tinea unguium, the compound represented by the general formula (1) has been desired to be solubilized in an amount twice or more the content of a general preparation for treating dermatomycosis, specifically, in an amount of 5% by mass or more, and it has been desired to develop a solvent to be used for solubilizing at a high concentration and formulating the compound represented by the general formula (1).
However, there was a situation in which only a few solvents could be used for producing a preparation containing such a compound at a high concentration because of its high crystallinity. That is, depending on the type of the solvent, there were some inconveniences, such as deposition of crystals at a low temperature such as 5° C. and deposition of crystals in application.
In addition, in a solution of luliconazole or the like, there exists a situation in which stereoisomers are easily produced. As a solvent to be used for preventing production of such stereoisomers, only crotamiton, propylene carbonate, and N-methyl-2-pyrroridone have been known (e.g., see Patent document 2). However, even such solvents have a problem such that blending has been limited in some cases depending on the inherent medicinal effects of the solvents, such as anti-inflammatory effects, and it has been desired to develop a novel solvent for formulation of luliconazole or the like as an alternative of the solvents.
where R1 and R2 each independently represent a hydrogen atom or a halogen atom, and at least one of R1 and R2 represents a halogen atom.
That is, in other words, it has been desired to develop a preparation having the following properties, which is a pharmaceutical composition for external use containing luliconazole or the like using a solvent other than crotamiton, propylene carbonate, and N-methyl-2-pyrroridone for solubilization and steric stabilization:
1) an amount of a stereoisomer of luliconazole or the like produced under a preservation condition of 60° C. for 3 weeks is 1% by mass or less with respect to a total mass of luliconazole or the like at the beginning of preservation;
2) the preparation is in a clear liquid state when preserved at a constant temperature of 20° C. immediately after manufacture; and
3) no crystal is deposited when the preparation is preserved at 5° C. for 2 weeks after manufacture.
Meanwhile, a higher alcohol which is in a liquid state at 1 atm and 25° C., such as isostearyl alcohol, a polyoxyethylene alkyl (or alkenyl)ether, and a diester of a dibasic acid such as diisopropyl adipate are known as components for drug formulation. Examples of a medicinal preparation containing the components in combination include ointments (e.g., see Patent document 3) and gels (e.g., see Patent documents 4, 5, 6, and 7). However, no solution-based preparation is known, and there is no example of their use for maintaining the steric structure of a compound.    [Patent document 1] WO 2007/102241    [Patent document 2] WO 2007/102242    [Patent document 3] JP 08-291049 A    [Patent document 4] JP 2005-298635 A    [Patent document 5] JP 2005-298388 A    [Patent document 6] JP 2006-232856 A    [Patent document 7] JP 2005-239678 A